The overall purpose of our research was to improve the tumor targeting properties of radiolabeled biologicals by optimizing chemical parameters. This year we developed a semi-automated 3-column system to purify a positron emitter, Y-86 because it is a better surrogate radionuclide than In-111 currently in use to estimate dosimetry of Y-90-labeled therapeutic radiopharmaceuticals. This purification system involved the passage of Cyclotron produced Y-86 samples through a Sr-selective Sr-Spec column, a Y-selective RE-Spec column and finally a cation-exchange Aminex A5 column connected in series. This method enabled us to decontaminate Sr by 250,000 times with >80% recovery of Y-86. We also investigated a new Tc-99m chemistry involving [Tc-99m (OH)3(CO)3]+ with Tc-99m (I) oxidation state to label biological molecules under mild conditions. The three water molecules of this complex are labile and can be substituted by a molecule with two or three coordination sites to form a stable ellipsoidal Tc-99m complex. We optimized the chemical condition to label norbiotinamido-DTPA, -benzylDTPA, -EDTA and ?succinimidoethylamino-(bis-ethylamine) with Tc-99m at 45?C and investigated the relationship between the polarity of the Tc-99m products and in vivo clearance kinetics. The biodistribution study in mice indicates that this approach is promising where further optimization of the polarity would produce a Tc-99m labeled biotin that rapidly accumulates in tumors with pretargeted antibody-streptavidin and is excreted via the renal system.